Recently, with coming of an aging society, the number of patients suffering from urinary frequency or urinary incontinence is increasing year by year. At present, as therapeutic drugs for urinary frequency or urinary incontinence, anticholinergic drugs such as propiverine hydrochloride, oxybutynin hydrochloride and flavoxate hydrochloride are used. However, it has been reported that these existing drugs have side effects, that is, dry mouth, gastrointestinal system symptoms such as constipation, cardiovascular symptoms such as orthostatic hypotension, urinary retention and residual urine. In addition, it is concerned that by administering the existing drugs having anticholinergic activities for the therapy of urinary frequency or urinary incontinence accompanied by cerebrovascular dysfunction or dementia, cholinergic system activity in the brain is inhibited, so that the cerebrovascular dysfunction or dementiaper se progress. On the other hand, from the view point of improving quality of life (QOL) of patients, which is recently regarded as important, urinary frequency and urinary incontinence are attracting attention as symptoms which should be positively cured. Thus, development of a therapeutic or prophylactic agent for urinary frequency or urinary incontinence without side effects is strongly demanded.
Morphinan derivatives having a nitrogen-containing heterocyclic group are described in Japanese Patent Publication Nos. 41-18824 and 41-18826 together with their uses as analgesics and antitussives, and in Tetrahedron. 50, 9757 (1994), Synth. Commun. 22, 913 (1992), J. Med. Chem. 27, 1325 (1984) which is silent about their uses. These patents and reference are silent about the use as a therapeutic or prophylactic agent for urinary frequency or urinary incontinence. Although it is known that morphine which is similar to the compounds of the present invention in the respect that it has morphinan structure although it does not contain a nitrogen-containing heterocyclic group has an activity to inhibit micturition reflex (J. Pharm. Exp. Ther. 254(1984) etc.), it has strong side effects such as drug dependence, constipation and so on, so that it is not used as a therapeutic or prophylactic agent for urinary frequency or urinary incontinence.